Design, Synthesis, and In Vitro Evaluation of Novel Histone H3 Peptide-Based LSD1 Inactivators Incorporating α,α-Disubstituted Amino Acids with γ-Turn-Inducing Structures.

Yosuke Ota, Taeko Kakizawa, Yukihiro Itoh, Takayoshi Suzuki

Open access · goldAbstract read

In one paragraph

Article in Molecules (Basel, Switzerland), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

0.4field-weighted citation impact, top 40% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 12 citations in OpenAlex.

Peptides as epigenetic modulators: therapeutic implications.Clinical epigenetics · 2019
Review

4 · The record

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5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Yosuke OtaDepartment of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-Cho, Sakyo-Ku, Kyoto 606-0823, Japan. y-ota@koto.kpu-m.ac.jp.

Taeko KakizawaDepartment of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo 169-8555, Japan. kg100683@kanto-gakuin.ac.jp.

Yukihiro ItohDepartment of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-Cho, Sakyo-Ku, Kyoto 606-0823, Japan. itohy@koto.kpu-m.ac.jp.ORCID 0000-0002-3410-2924

Takayoshi SuzukiDepartment of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-Cho, Sakyo-Ku, Kyoto 606-0823, Japan. suzukit@koto.kpu-m.ac.jp.ORCID 0000-0003-2439-879X

Kyoto Prefectural University of Medicine · JPWaseda University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lysine-specific demethylase 1 (LSD1) mainly removes methyl groups of mono- or di-methylated lysine residues at the fourth position of histone H3 to epigenetically regulate the expression of genes associated with several diseases, such as cancer. Therefore, LSD1 inactivators are expected to be used as therapeutic agents. In this study, to identify novel peptide-based LSD1 inactivators, we focused on the X-ray structure of LSD1 complexed with a H3 peptide-based suicide substrate. It has been proposed that a methylated histone substrate forms three consecutive γ-turn structures in the active pocket of LSD1. Based on this, we designed and synthesized novel histone H3 peptide-based LSD1 inactivators

Indexed as

Amino AcidsAmino Acids, CyclicCatalytic DomainCyclohexanecarboxylic AcidsDrug DesignEnzyme AssaysEnzyme InhibitorsHistone DemethylasesHistonesHumansHydrolysisIsoenzymesLysineMethylationMolecular Docking SimulationMonoamine Oxidase1-aminocyclohexanecarboxylic acidAmino AcidsAmino Acids, CyclicCyclohexanecarboxylic AcidsEnzyme InhibitorsHistone DemethylasesHistonesIsoenzymesKDM1A protein, humanLysineMonoamine OxidasePeptidesTranylcypromineepigeneticshistoneinhibitorlysine-specific demethylase 1 (LSD1)γ-turn structure

Identifiers

PMID29734782

DOI10.3390/molecules23051099

PMCPMC6099693

OpenAlexW2802026683

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.